Cell Dose and Immunogenetic Considerations in Cord Blood Transplantation

Abstract

Umbilical cord blood (CB) is a valuable alternative graft source for patients in need of allogeneic hematopoietic stem cell transplantation (HSCT) who lack suitable human leukocyte antigen (HLA)-matched related or unrelated donors and has extended allograft access to minority and mixed ancestry patients and those in need of urgent transplant. Compared to bone marrow (BM) or peripheral blood stem cell (PBSC) grafts from adult donors, CB offers the advantages of rapid availability, lack of risk to donor, less stringent requirements for HLA matching, and potent graft-versus-leukemia (GvL) effects. However, CB grafts contain a lower progenitor cell dose resulting in delayed myeloid engraftment, although the use of double-unit CBT (dCBT) has partially circumvented the limited cell dose extending transplant access to larger children and adults. CB grafts also do not transfer immune memory due to the naivety of CB T cells. This results in early infectious complications after CB transplantation (CBT). Over the last 25 years, due to advancements in CB banking, unit selection, conditioning regimens, immunosuppression, and supportive care, the outcomes of CBT have greatly improved. Moreover, disease-free survival (DFS) after CBT is comparable to other types of allografts in both pediatric and adult patients. CB graft characteristics (cell dose, HLA match to recipient, and post-thaw quality) are major determinants of engraftment with some studies also suggesting an effect on survival. In addition, the degree of HLA match has been shown to influence graft-versus-host disease (GvHD), as well as transplant-related mortality (TRM) and relapse risks. Other immunological factors such as direction of HLA mismatch, presence of donor-specific antibodies (DSA), non-inherited maternal antigens (NIMA) and inherited paternal antigens (IPA), and killer-cell immunoglobulin-like receptor (KIR) ligand (KIR-L) mismatch between unit and recipient have also been suggested to influence CBT outcomes but remain controversial. Thus, the primary factors that should dictate unit selection are CB cell dose and donor-recipient HLA match.